Pseudallescheria boydii is a rare cause of mycotic infection. Factors predisposing to systemic infection include traumas, immunosuppression, and near drowning. We report a case of multiple aneurysms caused by this hyalohyphomycete, occurred after near drowning. The car driven by a 53-year-old woman plunged into a canal in The Netherlands. After a 20-min-long submersion, the woman was rescued. At hospital, a severe aspiration of muddy water and a mycotic pneumonia were diagnosed. Despite the immediate prescription of a long-term antimycotic therapy and the initial good response, the patient died 4 months later. The autopsy showed a mycotic aneurysm of the abdominal aorta and multiple ruptured mycotic aneurysms of the circle of Willis with fatal subarachnoid bleeding.

The use of tracker dogs is the main method of finding hidden bodies, and in their search the dogs use typical scent patterns. "Electronic noses" can also be used to find and compare such patterns. Highly sensitive scent detectors have been successfully applied, e.g. in the examination of foodstuffs, in environmental tests and in material research. This study examined whether electronic sensors can be used to find bodies under outdoor conditions. The carcasses of two coneys were buried in soil at different depths. Over a period of 4 weeks, regular measurements were taken from the buried carcasses and from the control material. In addition, a "fingerprint" of the scent patterns was taken, and gas chromatography-mass spectrometry analyses were performed. Our findings indicate that it may be possible and viable to construct an "electronic body-tracking dog".

Dyskeratosis congenita (DC) is a multi-system disorder which in its classical form is characterised by abnormalities of the skin, nails and mucous membranes. In approximately 80% of cases, it is associated with bone marrow dysfunction. A variety of other abnormalities (including bone, brain, cancer, dental, eye, gastrointestinal, immunological and lung) have also been reported. Although first described almost a century ago it is the last 10 years, following the identification of the first DC gene (DKC1) in 1998, in which there has been rapid progress in its understanding. Six genes have been identified, defects in which cause different genetic subtypes (X-linked recessive, autosomal dominant, autosomal recessive) of DC. The products of these genes encode components that are critical for telomere maintenance; either because they are core constituents of telomerase (dyskerin, TERC, TERT, NOP10 and NHP2) or are part of the shelterin complex that protects the telomeric end (TIN2). These advances have also highlighted the connection between the more “cryptic/atypical” forms of the disease including aplastic anaemia and idiopathic pulmonary fibrosis. Equally, studies on this disease have demonstrated the critical importance of telomeres in human cells (including stem cells) and the severe consequences of their dysfunction. In this context DC and related diseases can now be regarded as disorders of “telomere and stem cell dysfunction”.

In a case of suicidal application of electricity differences between the rectal temperature of the body and the suspected time of death were observed.In order to answer the question whether an electric current from hand to hand over >30min led to a rise in body temperature FEM-based computer simulations and animal experiments were carried out. Both resulted in a warming of the soft parts in the arm without warming the body core. Thus a temperature-based estimation of the time since death can also be used in cases with electricity as the cause of death. Besides, in the animal experiment we found a spontaneous rise in the body core temperature even without application of electricity which may be a reason for the typical temperature plateau after death.

Although the bcr-abl translocation has been shown to be the causative genetic aberration in chronic myeloid leukemia (CML), there is mounting evidence that the deregulation of other genes, such as the transcription factor interferon regulatory factor 4 (IRF-4), is also implicated in the pathogenesis of CML. Promoter methylation of CpG target sites or direct deletions/insertions of genes are mechanisms of a reversible or permanent silencing of gene expression, respectively. Therefore, we investigated whether IRF-4 promoter methylation or mutation may be involved in the regulation of IRF-4 expression in leukemia cells. Whereas promoter mutations or structural rearrangements could be excluded as a cause of altered IRF-4 expression in hematopoietic cells, the IRF-4 promoter methylation status was found to significantly influence IRF-4 transcription. First, treatment of IRF-4-negative lymphoid, myeloid and monocytic cell lines with the methylation-inhibitor 5-aza-2-deoxycytidine resulted in a time- and concentration-dependent increase of IRF-4 mRNA and protein levels. Second, using a restriction-PCR-assay and bisulfite-sequencing we identified specifically methylated CpG sites in IRF-4-negative but not in IRF-4-positive cells. Third, we clearly determined promoter methylation as a mechanism for IRF-4 down-regulation via reporter gene assays, but did not detect an association of methylational status and mRNA expression of DNA methyltransferases or methyl-CpG-binding proteins. Together, these data suggest CpG site-specific IRF-4 promoter methylation as a putative mechanism of down-regulated IRF-4 expression in leukemia.

BACKGROUND:Reamed intramedullary nailing causes an increase of intramedullary pressure. A new rinsing-suction reamer (RSR) can reduce this problem, and it was evaluated in animal experiments in comparison with the AO reamer (AOR) to see its effects on intramedullary pressure and fat intravasation.METHODS:Reamed intramedullary nailing was performed in 14 sheep using the RSR or AOR. The following parameters were evaluated: intramedullary pressure, hemodynamics, blood tests, lung histology, and radiographs of the femur that was operated on.RESULTS:Intramedullary pressure during reaming was significantly (p < 0.001) lower with RSR (9 mm, 34 mm Hg; 9.5 mm, 4 mm Hg; 10 mm, 1 mm Hg) than AOR (9 mm, 750 mm Hg; 9.5 mm, 292 mm Hg; 10 mm, 138 mm Hg). There was a significantly (p < 0.05) higher increase of pulmonary resistance in AOR (from 144 +/- 84 dyne x s x cm to 391 +/- 169 dyne x s x cm) than in RSR (from 137 +/- 51 dyne x s x cm to 258 +/- 105 dyne x s x cm) after nailing and less intravenous fat measured in RSR (0.9; AOR, 2.9; p < 0.05) at all stages of reaming, at nail insertion (RSR, 0.3; AOR, 2.7; p < 0.05), and 30 seconds after nail insertion (RSR, 0.2; AOR, 1.1; p < 0.05) proved by the Gurd test. Pco2 increased (p < 0.05) in AOR (AOR, 36 +/- 5 vs. 40 +/- 7 mm Hg; RSR, 33 +/- 4 vs. 32 +/- 3 mm Hg) and pH dropped significantly (AOR, 7.49 +/- 0.06 vs. 7.45 +/- 0.05; RSR, 7.53 +/- 0.04 vs. 7.54 +/- 0.04; p < 0.05). Semiquantitative histologic analysis proved a significant higher pulmonary fat load in AOR (13.1 +/- 13.4) versus RSR (3.9 +/- 1.5, p = 0.00002).CONCLUSION:Because we found only a minimal increase of the pulmonary arterial pressure as a sign of pulmonary embolism, we conclude that by using the RSR, the systemic side effects caused by intravasation of medullary content during reaming could be reduced as far as possible.

The German study on sudden infant death (GeSID) is a multi-centre case-control study aiming at the assessment of etiological factors and risk factors of SIDS. This report describes the study design and the methods applied and presents some general findings. Between 1998 and 2001, 455 cases of sudden and unexpected death of infants aged between 8 and 365 days were recruited into the study. The study comprised at least 11 out of the 16 German states with 18 centres involved. In 1999 and 2000, 75% of all SIDS cases registered with the Federal Office of Statistics (ICD 10/R95, n=384) in the study area were recruited into the study (n=286). A standardised autopsy including extended histology, microbiology, virology, toxicology and neuropathology investigations was carried out. Of the parents 82% (n=373) agreed to fill in an extensive questionnaire containing 120 questions reflecting all important aspects of the infant’s development. For each SIDS case, the parents of three living control infants were interviewed. These controls were matched for age, gender and region (n=1,118). The response rate of the controls was 58.7%. Data were linked with medical records obtained from obstetrics departments, the children’s hospitals, and general practitioners. Death scene investigation was performed in 4 study areas (cases: n=64, controls: n=191). All cases were classified into one of 4 categories using defined criteria: 7.3% of the children were assigned to category 1 (no pathological findings: SIDS), 61.1% to category 2 (minor findings: SIDS+), 20.4% to category 3 (severe findings: SIDS+) and 11.2% to category 4 (findings which explained the death: non-SIDS). In case conferences the previous history and circumstantial factors were included and an extended category (E-cat.) was defined. The consideration of these factors for the final classification is of great importance in the causal explanation of some cases. An analysis of 18 main variables in cases of categories 1–3 (SIDS) compared to the cases of category 4 (non-SIDS) showed significant differences for the sleeping position, coughing the day before death and breast-feeding indicating that the cases of both groups should be separated for further analyses.

There are more than 120 different theories on the possible causes of sudden infant death (SID). In particular, dysfunctions of the central nervous system, cardiorespiratory insufficiency due to infections including atypical immune reactions, and cardiac dysregulation have been discussed during the previous decade. Reports on disturbances of the cardiac rhythmogenic function due to LQTS were among the most speculative. Based on gross histological, immunohistochemical and molecular genetic investigations of SID cases, the most important and most frequent findings of the heart are shown. The significance of different types of myocarditis, hypoxia-related changes, disturbances of the rhythmogenic function, cardiomyopathy, and other changes is discussed with regard to the cause of death. In conclusion, most of the changes reported in the literature are not sufficient to explain the cause of death. Problems in the diagnosis are shown which influence the classification of these disturbances as well as the classification of SID.

A sensitive method for the identification and quantitation of the organophosphate insecticide oxydemeton-methyl and its metabolite demeton-S-methylsulfon from human blood and various tissue samples has been established. After solid-phase extraction using C18 cartridges the extracts were analyzed by high-performance liquid chromatography with mass selective detection (Finnigan MAT LCQ). The method was completely validated. The limit of detection is 1 ng/g blood for the parent substance oxydemeton-methyl and 2 ng/g blood for the metabolite demeton-S-methylsulfon. This method was applied for the analysis of blood and tissue samples of a 58-year-old man who died after the intake of Metasystox R-Spezial, a product from Bayer containing oxydemeton-methyl. Because of a prolonged interval between the ingestion and death, the concentrations of oxydemeton-methyl and demeton-S-methylsulfon were very low. Although the body was already putrefied when the autopsy was performed, the chromatograms of blood and tissue samples were free of interfering peaks.

Use of intramedullary reamers (IR) is typically associated with pressure generation during the reaming process, which may result in the introduction of fat and marrow particles into the venous system. Thus, a new System was designed in order to avoid pressure generation and thus to reduce the risk of embolic events. In vitro testing was carried out using pig femura. Intramedullary pressure was recorded during drilling with either the new pressure-free intramedullary reamer (PF-IR; n = 10) or a Standard AO-IR (n = 10). For in vivo testing, nailing of the femur was performed in sheep using either the PF-IR (n = 7) or the Standard AO-IR (n = 7). Fat intravasation was measured using echocardiography and the Gurd test. Hemodynamic and pulmonary parameters as well as intramedullary pressure were continuously recorded during the experiments. The animals were then sacrificed and tissue samples were taken from all regions of the lungs. The incidence of lung fat emboli in histological sections was scored in a blinded manner. A finite element analysis was carried out to assess Performance of the PF-IR under load. The in vitro tests showed that the new PF-IR resulted in significantly less intramedullary pressure (15 ± 12 mm Hg) than the Standard AO-IR (813 ±247 mm Hg; p< 0.001, Mann-Whitney-U test). These results were confirmed in vivo. Moreover, the PF-IR group had significantly less fat intravasation (Gurd test) and better hemodynamic and pulmonary values than the AO-IR group. The incidence of fat microemboli in the lungs was reduced by 90% in the PF-IR group. Finite element analysis showed that the new drilling System performed well under load. The newly developed pressure-free IR clearly outperformed a Standard AO-IR. Use of the new PF-IR was associated with low intramedullary pressures, significantly less fat intravasation, and a markedly lower incidence of fat emboli in the lung. This, in turn, may have been the reason for the better hemodynamic and pulmonary values in the PF-IR group.

A 6-month-old male infant was treated with intravenous infusions and enteral feed via a naso-gastric tube. Accidentally, enteral feed containing pureed carrots diluted with water was injected intravenously and the child died immediately. Carrot material could be found in the pulmonary blood vessels and in various organs of the systemic circulation.

A fatal incident of an AB0 incompatible erythrocyte transfusion in a 75-year-old male patient who suffered from dilated cardiomyopathy with cardiac failure is reported. Blood group A red cells were transfused to the unintended recipient who had blood group 0. The patient died 45 min after the incompatible erythrocyte transfusion. The way the incident happened remained unclear and the immunohistochemical detection of AB0 incompatible erythrocytes in formaldehyde-fixed paraffin-embedded kidney, lung, liver and spleen tissue provided the only material evidence of the transfusion error.

Mitochondrial DNA control region sequences were determined in 1,200 male volunteers from one village area of Lower Saxony for the hypervariable region 1 (HV1). The 154 variable positions found resulted in 460 different haplotypes with a haplotype diversity value of 0.98165. The number of different haplotypes showed a nearly linear increase with the number of individuals typed. The haplotype diversity approached saturation level at a value of approximately 0.981 after typing 400 individuals. Furthermore, the number of different haplotypes and the haplotype diversity were calculated for four short amplicons of HV1 in order to establish the most variable section with a high efficiency for forensic casework.

Maltreatment of the elderly is a common problem that affects more than 3% of the elderly. We report on two cases of fatal neglect. Risk factors of victims and caregivers were analysed in the context of the social history. In both cases, the victims had a dominant personality and the abusers (the sons) had been strictly controlled and formed by the parent. The victims showed typical risk factors such as living together with the abuser, isolation, dependence on care, income and money administration. Initially, the victims declined help from outside and self-neglect occurred. The unemployed perpetrators lived in social isolation and depended financially and mentally on the victims. In both cases no mental illness was present but there was a decrease of social competence. Legal medicine is predominantly involved in fatal cases in connection with external post-mortem examinations and autopsies. Also in the living, the medico-legal expert can assist in the identification of findings in elderly persons in cases of suspected abuse.

In the two cases where infants died suddenly and unexpectedly the electrocardiogram (ECG) of a younger sibling (case 1) and of a living twin (case 2) led to the suspicion that the two infants could have died from long QT syndrome (LQTS). In case 1, a His bundle (HB) dispersion and a pronounced hypoplasia of the right external nucleus arcuatus were detected. In case 2, a severe interstitial pneumonia and an accompanying mild myocarditis were found by histology. Molecular genetic investigations of the coding regions of the genes, HERG, KVLQT1 and SCN5A gave no indication for the mutations, thus, affecting related myocardial ion channels as possible sources of inhomogeneity of repolarisation. Since a molecular genetic deviation could not yet be elaborated the possible role of related disturbance remains unknown.

Two series of experiments have been carried out on heart tissue for the occurrence of post-mortem and intravital myocardial damage. The first series was carried out on 18 porcine hearts collected immediately after the pigs were killed in a slaughterhouse. The hearts were subjected to stab wounds post-mortem, varying between 5 min and 140 min after death. The second series investigated were human hearts with intravital damage, i.e. 4 stab wounds, 1 gunshot, 13 contusions and ruptures. The time the trauma occurred before death varied between 0 and 30 min. The investigation comprised the four myocyte structural proteins myoglobin, FABP, troponin C, desmin and the three plasma proteins fibrinogen, fibronectin and C5b-9. Both series exhibited a variety of direct traumatic changes with a much broader zone in vital damage compared to post-mortem damage. In vital damage the zone of direct damage is in continuity with a further zone of indirect damage which is a three dimensional network. The signs of damage are contraction bands, depletion of structure antigens, contraction-associated accumulation of structure proteins, accumulation of plasma proteins on the cell surfaces and in the interstitium. In vital damages there is in addition an intrasarcolemmal accumulation of plasma proteins. The pattern of all damage is much broader and much more variegated in vital damage, thus vital damage can be clearly differentiated from post-mortem damage.

A 22-year-old white male was found dead at his working place in a car lacquering company. He had removed lacquer residues by using a solvent containing dicloromethane (DCM) without using a gas mask. Pathology revealed signs of asphyxiation with obvious petechial bleedings and expressed microthrombosis of the pulmonary arteries. Toxicological analysis showed excessive concentrations of DCM which are inhaled due to exposure of extreme air concentrations.

Mitochondrial DNA control region sequences were determined in 1200 male volunteers from one village area of Lower Saxony for the hypervariable region 1 (HV1). The 154 variable positions found resulted in 460 different haplotypes with a haplotype diversity value of 0.98165. The number of different haplotypes showed a nearly linear increase with the number of individuals typed. The haplotype diversity approached saturation level at a value of approximately 0.981 after typing 400 individuals. Furthermore, the number of different haplotypes and the haplotype diversity were calculated for four short amplicons of HV1 in order to establish the most variable section with a high efficiency for forensic casework.

The study was undertaken to evaluate the kinetics and distribution patterns of several immunohistochemical markers in ischemically and hypoxically damaged myocardium. The myocardium of 8 cases of acute myocardial infarction (AMI), 8 cases of diagnosed acute cardiac death (ACD) and 12 cases of acute exogenic hypoxia (AEH) due to CO poisoning or hanging were analysed for depletion of the cardiac antigens FABP, troponin C and T, desmin and myoglobin, loss of CD59 and deposition of the plasma antigens fibrinogen, fibronectin and the terminal complement complex C5b-9. The visualisation of the terminal complement complex was positive as early as 30 min after onset of symptoms of AMI. Depletion of cellular antigens started earlier than the deposition of plasma antigens. The deposition of fibronectin and fibrinogen began earlier than the detection of C5b-9 but later than the depletion of the cellular antigens. Our findings indicate that for the immunohistochemical detection of very early myocardial damage, the depletion of myoglobin is at least of the same rank or better than depletion of FABP and troponin.